Process for the preparation of N-monosubstituted carbamic acid esters

ABSTRACT

A process for the preparation of N-monosubstituted carbamic acid esters by reacting an unsubstituted carbamic acid ester and an aromatic primary amine at a suitable pressure and reaction temperature in the presence of a monohydric aliphatic alcohol and preferably in the presence of a strongly basic tertiary amine as catalyst. Optionally an inert co-solvent in addition to the alcohol may be employed.

BACKGROUND OF THE INVENTION

U.S. Pat. No. 3,161,676 describes a process for the preparation of asubstituted alkyl urea by reacting a carbamic acid ester with a primaryand sterically unhindered secondary aliphatic amines in the presence ofa metal compound Lewis acid catalyst, such as cupric acetate.

There is no known prior art which describes the preparation ofN-monosubstituted carbamic acid esters by reacting an unsubstitutedcarbamic acid ester and an aromatic primary amine in the presence of amonohydric aliphatic alcohol with or without the use of a tertiary aminecatalyst.

Many important commercial applications have been developed for thecarbamic acid ester products of this invention, for example, asagricultural chemicals and chemical intermediates which may be convertedto the corresponding isocyanate and alcohol by thermal decomposition orother methods described in the prior art.

SUMMARY OF THE INVENTION

The present invention is based on the unexpected discovery that it ispossible to produce, in high yield and high conversions of reactants, anN-substituted carbamate, such as ethylphenylcarbamate (ethylN-phenylcarbamate), by the reaction of an aromatic primary amine such asaniline with an unsubstituted carbamate such as ethyl carbamate at atemperature of from about 125° C. to 250° C. in the presence of amonohydric aliphatic alcohol and preferably in the presence of atertiary amine catalyst. While the alcohol employed may, among otherthings, function as a solvent to effect the reaction, a co-solvent inaddition to the alcohol may alternatively be used in the process of theinvention.

It is a primary object of this invention therefore, to provide a novelprocess for the preparation of N-monosubstituted carbamates.

It is another object of this invention to provide a novel reactionsystem for the conversion of an unsubstituted carbamic acid ester and anaromatic primary amine to N-monosubstituted carbamic acid esters, suchas ethylphenylcarbamate.

These and other objects and advantages of this invention will becomeapparent from the description of the invention which follows, and fromthe claims.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with this invention an N-substituted carbamic acid esteris produced by reacting an unsubstituted carbamic acid ester of thegeneral formula NH₂ CO₂ R wherein R is a straight or branched chainalkyl group containing from 1 to 10 carbon atoms, with a primaryaromatic amine of the general formula R'(NH₂)n wherein R' may be asubstituted or unsubstituted aryl or aralkyl group containing one ormore benzenoid rings, preferably not more than six, which may be fusedor joined by single valency bonds, directly or through bridging groupswhich may be, for example, oxygen or sulfur or a methylene group at atemperature in the range of from about 125° C. to 250° C. in thepresence of a monohydric aliphatic alcohol having from 1 to 10 carbonatoms and preferably in the presence of a tertiary amine catalyst.Alternatively an inert solvent in addition to the alcohol may beemployed. The R and R' may also contain substituents which do notinterfere with the reaction, such as alkoxy, sulfur, sulfoxide, sulfone,etc. radicals. n is an integer of 1 to 6.

The reaction between the unsubstituted carbamic acid ester and thearomatic primary amine may be carried out in any suitable reactor, suchas an autoclave, which is generally equipped with a means for agitation,means for regulating temperature and pressure and means for removingby-product ammonia, and possibly alcohol vapor. Although the order ofaddition of the reactants, alcohol and solvents and catalyst components,if any, may vary, a general procedure for carrying out the reaction isto charge the unsubstituted carbamic acid ester, primary aromatic amine,alcohol and, preferably, a strongly basic tertiary amine catalyst intothe reaction vessel and then heat the mixture to the desired temperatureat atmospheric pressure or higher pressures, if required. The reactioncan be carried out batchwise, semicontinuous, or as a continuousprocess. The reaction products are recovered and treated by anyconventional method, such as distillation or fractionation to effectseparation of the N-monosubstituted carbamate from unreacted startingmaterial, catalyst, solvent and by-products.

The unsubstituted carbamic acid esters employed as reactants in theprocess of the present invention conform to the general formula NH₂ CO₂R wherein R is a substituted or unsubstituted straight or branched chainalkyl group containing from 1 to 10 carbon atoms. Representativeunsubstituted carbamic acid esters suitable for use in this inventioninclude, for example, methyl carbamate, ethyl carbamate, normal andisobutylcarbamates, propyl carbamate, amyl carbamate, isoamyl carbamate,hexyl carbamate, octyl carbamate, 2-ethylhexyl carbamate, decylcarbamates, heptyl carbamate, nonyl carbamate, 2 ethyl-1-butylcarbamate, 3,5-dimethyl-1-hexyl carbamate, and the like. In general, themethyl and ethyl esters and more readily available and are, therefore,more preferred.

The aromatic primary amines employed as reactants in the process of thepresent invention conform to the general formula R'(NH₂)n wherein R' isa substituted or unsubstituted aryl or aralkyl group containing one ormore benzenoid rings, preferably not more than six, which may be fusedor joined by single valency bonds directly or through bridging groupswhich may be, for example, oxygen or sulfur or a methylene group; n is 1to 6. Representative amines as hereinabove described include, forexample, aniline, toluidines, naphthylamines, benzylamines, xylidines,xylene diamines, naphthalene diamines, toluene diamines, xylylyenediamines, anisidines, phenetidines, 3,3'-dimethyl-4,4'-diphenyldiamine,phenylenediamines, 2,4'- and 4,4'-methylenedianiline,sulfonyldianilines, dimethylbenzylamine, naphthalenemethylamines,dimethyl and diethylbenzidines, methyl and ethylthioanilines,biphenylamines and diamines, phenoxyanilines, thiodianilines, and thelike. The polyamine made by condensing aniline with formaldehyde andused, for example, in the preparation of polymeric isocyanates may alsobe employed. In general, aniline and the toluene diamines are preferred.

The alcohols which are employed are monohydric aliphatic alcoholscontaining from 1 to 10 carbon atoms. It is generally preferred that thealcohol employed correspond to the alkyl group of the reactantunsubstituted carbamic acid ester in order to prevent the preparation ofmixed N-substituted carbamates. The alcohols, in addition to acting asthe reaction solvent, substantially inhibit side reactions and aregenerally employed in a molar excess based on the amine or unsubstitutedcarbamic acid ester reactants, i.e., from about a molar ratio of 0.5:1to 15:1 of alcohol to amine or carbamate reactant employed to producethe N-substituted carbamic acid esters. Representative alcohols whichmay be employed in the process of this invention include, for example,methanol, ethanol, n-propanol, n- and iso-butyl alcohols, amyl alcohol,hexanol, heptanol, octanol, nonanol, decanol, 2-ethyl hexanol, 2-methylpentanol, 2-ethyl-1-butanol, 3,5-dimethyl-1-hexanol, and the like. Thelower aliphatic alcohols having 1 to 4 carbon atoms are preferred.

A general postulated equation for the reaction of the present inventionmay be represented as follows: ##STR1## wherein R and R' are ashereinabove described. A wide variety of N-substituted carbamates can beprepared by the process of this invention.

Although an optional feature of this invention, it has also beendiscovered that improved yields and increased reaction rates can beobtained when the above reaction is carried out in the presence of astrongly basic tertiary amine catalyst. The tertiary amine catalysts maybe an aliphatic, cycloaliphatic, araliphatic or aromatic aminecontaining from 1 to 18 carbon atoms, which may be interrupted byoxygen, sulfur, nitrogen, sulfoxide or carbonyl substituents. Ingeneral, the amine employed as catalyst should be easily separated fromreaction product and by-products. Representative amines suitable for usein the process of the invention include, for example, the trialkylaminessuch as the trimethyl, triethyl, tripropyl, tributyl, trihexyl,trioctyl, tridecyl, tridodecyl, etc. amines, triphenylamine,n-dodecyldimethylamine, n-tetradecyldimethylamine,n-hexyldecyldimethylamine, n-octyldecyldimethylamine,N,N,N',N'-tetramethylethylenediamine, N,N-dioctyl-1-octylamine,1,4-diazabicyclo[2.2.2]octane, 4(N,N-dimethylamino) pyridine, pyridine,1,5-diazabicyclo[3.4.0]non-5-ene, 1,8-diazabicyclo[5.4.0]-undec-7-ene,1,1,3,3-tetramethylbutylamine, methyldiethylamine, butyldimethylamine,benzyldimethylamine, and the like. The amount of tertiary amine catalystwhich can be used in the process will generally range between about 0.01to 30 mole percent, preferably 0.1 to 20 mole percent based on thearomatic primary amine employed in the reaction, but greater or lesserquantities may be used if desired.

Although the process of the invention is preferably carried out usingthe monohydric aliphatic alcohol as the reaction solvent, other solventsor mixtures of solvents which are stable and substantially chemicallyinert to the components of the reaction system may be employed as aco-solvent in the reaction system if desired. Suitable co-solvents whichmay be employed, and generally in amounts of from 0 to 50 weight percentbased on the reaction mixture, include, for example, benzene, toluenes,xylenes, dichlorobenzene, tetrahydrofuran, 1,2-dimethoxyethane,diphenylether, nitrobenzene, diethyleneglycol dimethyl ether,triethyleneglycol dimethyl ether, dimethylsulfoxide, and the like.

The ratio of reactants, i.e., unsubstituted carbamic acid ester andaromatic primary amine may be varied over any convenient range. The moleratio of amine to unsubstituted carbamate may be between about 10:1 to0.1:1 and is preferably between about 5:1 to 0.25:1.

The reaction of the present invention will proceed at temperatures offrom about 125° C. to 250° C. It is generally preferred to operate theprocess at temperatures of from about 175° C. to 225° C. to obtain aconvenient rate of reaction. The reaction temperature will depend on theparticular N-substituted carbamic acid ester being produced and shouldbe below the temperature at which significant decomposition of theproduct ester might occur.

The process of the present invention is generally carried out atatmospheric pressure, although higher pressures of up to 50 atmospheresmay be used and especially at the higher reaction temperatures or whenthe reaction temperature is above the boiling point of the alcoholand/or reactant amine. Subatmospheric pressures may be employed, ifdesired.

Ammonia resulting from the reaction must be removed during the course ofthe reaction, otherwise reduced yields of product carbamate areobtained. When the reaction is carried out at one atmosphere the ammoniais simply allowed to escape from the reaction vessel. In reactions whereelevated pressures are employed provisions must be made to removeammonia. A simple, convenient method is to strip the ammonia from thereactor with a dry inert gas, such as nitrogen or carbon dioxide and/orwith the resulting alcohol vapor provided the alcohol employed isvolatile at the reaction temperature. When the alcohol vapor is used tostrip or aid in stripping the ammonia from the reactor, additional ormakeup alcohol can be added to the reactor at a rate to compensate forthe vapor loss.

The reaction time is generally dependent on the N-monosubstitutedcarbamate being produced, the reaction temperature and the catalystemployed, if any, and will vary depending on whether the process ifcontinuous or batch but will generally range between about one toseveral hours.

The following Examples are provided to illustrate the invention inaccordance with the principles of this invention, but are not to beconstrued as limiting the invention in any way except as indicated bythe appended claims.

In the Examples which follow, the reactions were run in a 300 mlstainless steel stirred autoclave. The amine, unsubstituted carbamicacid ester and alcohol, along with tertiary amine catalyst andco-solvent, if any, are charged to the reactor which is then flushedwith nitrogen and the reactor heated to the desired reaction temperaturefor a specified time period. During the reaction vaporized alcohol andproduct ammonia are stripped from the reactor with or without the aid ofan inert gas. Makeup alcohol is pumped into the reactor at a rateclosely approximating the alcohol removed. At the end of the reactiontime, the autoclave is cooled to ambient temperature and the contentscombined with the stripped alcohol which was collected in a dry icecooled trap and the total mixture analyzed by liquid chromatography (LC)for conversion of amine and unsubstituted carbamic acid ester andselectivities to N-monosubstituted carbamate. Amine and theunsubstituted carbamate conversions were calculated on the basis ofmoles of the amine and carbamate consumed by the reaction. Productselectivities were based on the moles of amine or unsubstitutedcarbamate consumed in preparing the N-monosubstituted carbamate andby-products.

EXAMPLE 1

23.3 g aniline, 22.2 g ethyl carbamate and 220 ml of dry ethanol (200proof) was charged to the autoclave which was flushed several times withnitrogen and heated to 200° C. for a period of 3 hours. During thereaction period ethanol and ammonia were stripped from the reactor withnitrogen at an average of 1.7 ml of ethanol per minute. The ethanolvapor containing ammonia and a small amount of aniline was condensed ina dry ice cooled trap. Makeup ethanol was pumped into the autoclave at arate closely approximating the amount stripped. After the reactionperiod, the autoclave was cooled and the contents along with the ethanolcondensate analyzed. LC analysis showed an aniline conversion of 34percent and an ethylcarbamate conversion of 47.2 percent withselectivities to ethylphenylcarbamate of 79 mole percent and 47.2 molepercent based on aniline and ethylcarbamate, respectively.

EXAMPLE 2

Example 1 was repeated using 100 ml ethanol and 100 ml benzeneco-solvent. Analysis of the product and ethanol condensate showed ananiline conversion of 54 percent and an ethylcarbamate conversion of 65percent. Selectivities to ethylphenylcarbamate was 75 mole percent and62 mole percent based on aniline and ethylcarbamate, respectively.

EXAMPLE 3

Example 1 was repeated using 0.76 g 1,8-diazabicyclo[5.4.0]undec-7-eneas catalyst. Analysis showed an aniline conversion of 62.4 percent andan ethylcarbamate conversion of 84 percent with selectivities toethylphenylcarbamate of 96.5 mole percent and 71 percent based onaniline and ethylcarbamate, respectively.

EXAMPLE 4

Example 2 was repeated using 100 ml diphenylether as a co-solvent, alongwith 0.4 mole of pyridine as catalyst. Analysis showed an anilineconversion of 55 percent and an ethylcarbamate of 66 percent withselectivities to ethylphenylcarbamate based on aniline andethylcarbamate of 92 and 86 mole percent, respectively.

EXAMPLES 5 TO 23

In Examples 5 to 23, which follow in Table form, the general procedureas hereinabove described was repeated using various amines,unsubstituted carbamic acid esters, alcohols, tertiary amine catalystsand conditions as shown in Table 1. The results are set forth in Table2.

                                      TABLE 1                                     __________________________________________________________________________    Charge (Moles)                                                                Example       Unsubstituted              Conditions                           No.  Amine    Carbamate  Alcohol Catalyst                                                                              Temperature                                                                          Time                          __________________________________________________________________________    5.   Aniline                                                                              .25                                                                             Ethyl carbamate                                                                        .25                                                                             Ethanol                                                                            3.8                                                                                --    150° C.                                                                       4 hrs                         6.   Aniline                                                                              .25                                                                             Ethyl carbamate                                                                        .25                                                                             Ethanol                                                                            3.8                                                                                --    200° C.                                                                       3 hrs                         7.   Aniline                                                                              .25                                                                             Ethyl carbamate                                                                        .25                                                                             Ethanol                                                                            3.8                                                                              DBU.sup.(1)                                                                        .006                                                                             200° C.                                                                       3 hrs                         8.   Aniline                                                                              .25                                                                             Ethyl carbamate                                                                        .25                                                                             Ethanol                                                                            1.7                                                                              DBU  .006                                                                             200° C.                                                                       3 hrs                         9.   Aniline                                                                              .75                                                                             Ethyl carbamate                                                                        .05                                                                             Ethanol                                                                            2.2                                                                              DBU  .005                                                                             200° C.                                                                       3 hrs                         10.  Aniline                                                                              .75                                                                             Ethyl carbamate                                                                        .05                                                                             Ethanol                                                                            1.1                                                                              DBN.sup.(2)                                                                        .005                                                                             200° C.                                                                       2 hrs                                                          Pyridine                                                                           .83                                     11.  Aniline                                                                              .64                                                                             Ethyl carbamate                                                                        .64                                                                             Ethanol                                                                            1.8                                                                              DBN  .006                                                                             200° C.                                                                       3 hrs                         12.  Aniline                                                                              .54                                                                             Ethyl carbamate                                                                        .54                                                                             Ethanol                                                                            2.2                                                                              TOA.sup.(3)                                                                        .005                                                                             200° C.                                                                       3 hrs                         13.  Aniline                                                                              .64                                                                             Ethyl carbamate                                                                        .64                                                                             Ethanol                                                                            2.7                                                                              TOA  .06                                                                              200° C.                                                                       2 hrs                         14.  Aniline                                                                              .64                                                                             Ethyl carbamate                                                                        .64                                                                             Ethanol                                                                            2.4                                                                              Pyridine                                                                           .4 200° C.                                                                       3 hrs                         15.  Aniline                                                                              .64                                                                             Ethyl carbamate                                                                        .64                                                                             Ethanol                                                                            0.85                                                                             TEA.sup.(4)                                                                        .68                                                                              200° C.                                                                       3 hrs                         16.  Aniline                                                                              .64                                                                             Ethyl carbamate                                                                        .64                                                                             Ethanol                                                                            2.7                                                                              TPA.sup.(5)                                                                        .003                                                                             200° C.                                                                       2 hrs                         17.  Aniline                                                                              .64                                                                             Ethyl carbamate                                                                        .64                                                                             Ethanol                                                                            2.7                                                                              TPA  .06                                                                              200° C.                                                                       3 hrs                         18.  Aniline                                                                              .64                                                                             Methyl carbamate                                                                       .64                                                                             Methanol                                                                           3.2                                                                              TEA  .1 200° C.                                                                       3 hrs                         19.  β-Naphthyl-                                                                       Methyl carbamate                                                                       .64                                                                             Methanol                                                                           3.5                                                                              DBU  .006                                                                             200° C.                                                                       3 hrs                              amine  .64                                                               20.  2,4-Toluene-                                                                           Ethyl carbamate                                                                        .64                                                                             Ethanol                                                                            3.0                                                                              DBN  .005                                                                             200° C.                                                                       3 hrs                              Diamine                                                                              .32                                                               21.  Aniline                                                                              .64                                                                             Octyl carbamate                                                                        .64                                                                             Octanol                                                                            2.7                                                                              TEA  .5 200° C.                                                                       3 hrs                         22.  Aniline                                                                              .64                                                                             Ethyl carbamate                                                                        .64                                                                             Ethanol                                                                            3.0                                                                              TEA  .3 175° C.                                                                       3 hrs                         23.  Aniline                                                                              .64                                                                             Ethyl carbamate                                                                        .64                                                                             Decanol                                                                            3.0                                                                              TEA  .68                                                                              210° C.                                                                       2 hrs                         __________________________________________________________________________     .sup.(1) DBU 1,8Diazabicyclo[5.4.0]undec7-ene                                 .sup.(2) DBN 1,5Diazabicyclo[4.3.0]non 5ene                                   .sup.(3) TOA Trin-octylamine                                                  .sup.(4) TEA Triethylamine                                                    .sup.(5) TPA Trin-propylamine                                            

                  TABLE 2                                                         ______________________________________                                        Amine              Unsubstituted Carbamate                                    Ex-  Mole     Mole Percent Mole   Mole Percent                                am-  Percent  N--mono-substi-                                                                            Percent                                                                              N--mono-substi-                             ple  Con-     tuted Carbamate                                                                            Con-   tuted Carbamate                             No.  version  Selectivity  version                                                                              Selectivity                                 ______________________________________                                        5.   30       EPC.sup.(6)                                                                            60    29     EPC.sup.(6)                                                                          65                                 6.   34       EPC      79    47     EPC    58                                 7.   46       EPC      86    59     EPC    67                                 8.   61       EPC      97    85     EPC    71                                 9.   55       EPC      87    82     EPC    88                                 10.  61       EPC      73    95     EPC    70                                 11.  67       EPC      95    69     EPC    93                                 12.  54       EPC      92    49     EPC    100                                13.  57       EPC      82    61     EPC    78                                 14.  55       EPC      92    59     EPC    85                                 15.  86       EPC      92    89     EPC    90                                 16.  21       EPC      97    20     EPC    98                                 17.  38       EPC      78    43     EPC    66                                 18.  62       MPC.sup.(7)                                                                            85    64     MPC.sup.(7)                                                                          83                                 19.  50       MNC.sup.(8)                                                                            87    55     MNC.sup.(8)                                                                          79                                 20.  85       DETC.sup.(9)                                                                           90    45     DETC.sup.(9)                                                                         85                                 21.  56       OPC.sup.(10)                                                                           80    58     OPC.sup.(10)                                                                         77                                 22.  24       EPC      96    29     EPC    91                                 23.  48       EPC      85    57     EPC    68                                 ______________________________________                                         .sup.(6) EPC Ethylphenyl carbamate                                            .sup.(7) MPC Methylphenyl carbamate                                           .sup.(8) MNC Methylnaphthyl carbamate                                         .sup.(9) DETC 2,4diethyltolyldicarbamate                                      .sup.(10) OPC octylphenyl carbamate                                      

We claim:
 1. A process for the preparation of an N-monosubstitutedcarbamic acid ester which comprises reacting an unsubstituted carbamicacid ester having the formula NH₂ CO₂ R wherein R is a straight orbranched chain alkyl group containing from 1 to 10 carbon atoms, with anaromatic primary amine having the formula R'(NH₂)n wherein R' is asubstituted or unsubstituted aryl or aralkyl group containing one ormore benzenoid rings which may be fused or joined by single valencybonds and n is an integer of 1 to 6, at a temperature in the range offrom about 125° C. to 250° C. in the presence of a monohydric aliphaticalcohol having from 1 to 10 carbon atoms and a catalytic amount of fromabout 0.01 to 30 mole percent based on the aromatic primary amineemployed of a tertiary amine which may be an aliphatic, cycloaliphatic,aryliphatic or aromatic amine containing from 1 to 18 carbon atoms.
 2. Aprocess according to claim 1 wherein the unsubstituted carbamic acidester is selected from the group consisting of methylcarbamate,ethylcarbamate, and octylcarbamate.
 3. A process according to claim 2wherein the unsubstituted carbamic acid ester is ethyl carbamate.
 4. Aprocess according to claim 1 wherein the aromatic primary amine isselected from the group consisting of aniline, toluene diamines andnaphthylamines.
 5. A process according to claim 4 wherein the aromaticprimary amine is aniline.
 6. A process according to claim 1 wherein thereactant aromatic primary amine to unsubstituted carbamic acid ester isemployed at a molar ratio of from about 10:1 to 0.1:1.
 7. A processaccording to claim 6 wherein the molar ratio employed is from about 5:1to 0.25:1.
 8. A process according to claim 1 wherein the alcohol isemployed at a molar ratio of from about 0.5:1 to 15:1 based on the amineor unsubstituted carbamic acid reactant.
 9. A process according to claim1 wherein the monohydric aliphatic alcohol is selected from the groupconsisting of methanol, ethanol, octanol and decanol.
 10. A processaccording to claim 9 wherein the alcohol is ethanol.
 11. A processaccording to claim 9 wherein the alcohol is methanol.
 12. A processaccording to claim 1 wherein the tertiary amine is employed in acatalytic amount of from 0.1 to 20 mole percent of the aromatic primaryamine employed.
 13. A process according to claim 1 wherein the tertiaryamine is selected from the group consisting of triethylamine,tri-n-propylamine, tri-n-octylamine, pyridine,1,5-diazabicyclo[4.3.0]non-5-ene and 1,8-diazabicyclo[5.4.0]undec-7-ene.14. A process according to claim 13 wherein the tertiary amine istriethylamine.
 15. A process according to claim 13 wherein the tertiaryamine is pyridine.
 16. A process according to claim 13 wherein thetertiary amine is 1,8-diazabicyclo[5.4.0]undec-7-ene.
 17. A processaccording to claim 1 wherein the reaction temperature is in the range offrom about 175° C. to 225° C.
 18. A process according to claim 1 whereinthe reaction is carried out under a pressure of from 1 to 50atmospheres.
 19. A process according to claim 1 wherein the reaction iscarried out in the presence of an inert solvent in addition to thealcohol.
 20. A process for the preparation of ethylphenylcarbamate whichcomprises reacting ethylcarbamate with aniline at a temperature of fromabout 175° C. to 225° C. at a molar ratio of aniline to ethylcarbamatein the range of from 5:1 to 0.25:1 in the presence of ethyl alcohol anda catalytic amount of from 0.1 to 20 mole percent triethylamine.
 21. Aprocess according to claim 20 wherein the reaction is carried out in thepresence of an inert solvent.